dictyNews
Electronic Edition
Volume 49, number 23
September 22, 2023

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Abstracts
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Loss of mfsd8 alters the secretome during Dictyostelium aggregation

Robert J. Huber (1), Joshua Gray (2), and William D. Kim (2)

(1) Department of Biology, Trent University, Peterborough, Ontario, 
Canada
(2) Environmental and Life Sciences Graduate Program, Trent 
University, Peterborough, Ontario, Canada


European Journal of Cell Biology, accepted

Major facilitator superfamily domain-containing protein 8 (MFSD8) 
is a transmembrane protein that has been reported to function as a 
lysosomal chloride channel. In humans, homozygous mutations in 
MFSD8 cause a late-infantile form of neuronal ceroid lipofuscinosis 
(NCL) called CLN7 disease. In the social amoeba Dictyostelium 
discoideum, Mfsd8 localizes to cytoplasmic puncta and vesicles, and 
regulates conserved processes during the organism's life cycle. Here, 
we used D. discoideum to examine the effect of mfsd8-deficiency on 
the secretome during the early stages of multicellular development. 
Mass spectrometry revealed 61 proteins that were differentially 
released by cells after 4 and 8 hours of starvation. Most proteins 
were present in increased amounts in mfsd8- conditioned buffer 
compared to WT indicating that loss of mfsd8 deregulates protein 
secretion and/or causes the release of proteins not normally secreted 
by WT cells. GO term enrichment analyses showed that many of the 
proteins aberrantly released by mfsd8- cells localize to compartments 
and regions of the cell associated with the endo-lysosomal and 
secretory pathways. Mass spectrometry also revealed proteins 
previously known to be impacted by the loss of mfsd8 
(e.g., cathepsin D), as well as proteins that may underlie mfsd8-
deficiency phenotypes during aggregation. Finally, we show that 
mfsd8-deficiency reduces intracellular proteasome 20S activity due 
to the abnormal release of at least one proteasomal subunit. Together, 
this study reveals the impact of mfsd8 loss on the secretome during 
D. discoideum aggregation and lays the foundation for follow up work 
that investigates the role of altered protein release in CLN7 disease.


Submitted by Robert Huber [[log in to unmask]]
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[End dictyNews, volume 49, number 23]